Known in the art is a crystalline modification of 2-dimethylaminoethyl-n-butylaminobenzoate hydrochloride (tetracaine), polymorphic form (R. C. Sullivan, K. P. O'Brien. X-ray diffraction studies of cocaone and its substitutes.--Bull.Narcotics, 1968, V.20, pp. 31--40), characterized, by the following set of interplanar spacings d and relative intensities of reflections I:
______________________________________ d, .ANG. I ______________________________________ I2.55 I00 8.38 42 6.28 I2 5.42 8 5.05 67 4.83 I2 4.43 8 4.22 20 3.97 II 3.78 I0 3.56 8 3.48 I7 3.30 I0 3.I2 I0 2.96 6 2.805 7 2.66I 5 2.507 5 2.I5I 4 I.949 4 ______________________________________
Also known in the art is a crystalline modification of 2-dimethylaminoethyl-n-butylaminobenzoate hydrochloride (amethocaine), polymorphic form (I. T. R. Owen, R. Sithiraks, F. A. Underwood. X-ray powder diffraction data for seventeen local anesthetics--I.Ass.Off Analyt. Chem., 1972, V.55) characterized by the following set of interplanar spacings d and relative intensities of reflections I:
______________________________________ d, .ANG. I d, .ANG. I ______________________________________ I3.3 I0 3.22 7 8.06 I0 3.I7 I0 6.55 40 3.08 9 6.23 20 3.03 7 6.02 40 3.00 7 5.73 6 2.94 4 5.07 6 2.87 6 4.78 I5 2.82 I2 4.50 25 2.77 9 4.39 I3 2.7I 6 4.23 20 2.66 7 4.05 I5 2.62 6 3.98 I8 2.58 6 3.83 25 2.54 7 3.73 I2 2.50 4 3.65 I00 2.46 6 3.57 I0 2.42 6 3.45 20 2.32 6 3.40 7 2.28 6 3.28 6 2.24 6 2.I5 6 ______________________________________
Melting point of specified modifications is in the range of from 147.degree. to 15.degree. C. In this case, the process of melting of these modifications is a sequence of two endothermal effects (R. Curini, S. Zamponi, F. D'Ascenzo, S. De Angelis Curtis, A. Marino, A. Dezzi, Thermal analytical techniques applied to the narcotic field: cocaine analysis.--Thermochim. Acta, 1989, V.153, N I, pp. 11-26).
Known in the art is a method for production of said modifications of 2-dimethylaminoethyl-n-butylaminobenzoate hydrochloride, comprising a process of n-butylation of .beta.-dimethylaminoethyl-para-aminobenzoate with subsequent crystallization of the obtained product in the mixture with hydrosulfite and carbon from ethyl alcohol at 2.degree.-3.degree. C. and drying (Synthetic chemico-pharmaceutical preparations, "Meditsina", (Moscow), 1971, pp. 75-77)
The obtained product represents the aforementioned crystalline modifications characterized by the specified set of values d and I. Melting point of the obtained compound is in the range of 147.degree.-15.degree. C. with two subsequent endothermal effects.
The obtained product is a white crystalline powder having a slightly bitter taste, which causes temporary anaesthesia of the tongue, soluble in water and alcohol, moderately soluble in chloroform and practically insoluble in ether.
The known crystalline modifications of said compound, showing an effect of local anaesthesia, are highly toxic.
Besides, the known modifications of said compound have considerable side effects and when pharmaceutical preparations based on these compounds are used in ophthal-mosurgery, they cause eyelid edema, injury to cornea epithelium, erosions, considerable dilation of conjuctiva. Eye drops based on these compounds are unstable in storage (term of validity is 3 months on condition of additional stabilization of the solution).
The crystalline modification of 2-dimethylaminoethyl-n-butylaminobenzoate hydrochloride according to the invention, method of its production and application are novel and haven't been described in the literature.